Abstract
BACKGROUND: Total parenteral nutrition (TPN) is widely used after major gastrointestinal surgery; however, its early systemic metabolic effects and temporal adaptation patterns remain incompletely characterized. This study applied a longitudinal plasma metabolomics approach to investigate time-dependent metabolic changes during early TPN administration. METHODS: Plasma samples were collected from patients undergoing gastrointestinal surgery before TPN initiation (baseline, T0) and at 24 h (T1), 48 h (T2), and 72 h (T3). Untargeted metabolomic profiling was performed using complementary gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) platforms. In total, 111 metabolites were detected. Analysis of variance (ANOVA) with baseline (T0) as the reference identified time-point-specific metabolic alterations during TPN administration. RESULTS: At 24 h (T1), nominally significant increases were observed in glycine, tryptophan, isoleucine, and methionine, accompanied by decreases in sarcosine and oxalic acid. At 48 h (T2), elevated levels of glycine, isoleucine, valine, and phenylalanine persisted, while sarcosine, oxalic acid, and myo-inositol remained decreased. By 72 h (T3), sustained increases in glycine, isoleucine, valine, phenylalanine, proline, alanine, and tryptophan were accompanied by reduced levels of sarcosine, oxalic acid, and glucopyranose, reflecting coordinated alterations across multiple metabolite classes. CONCLUSIONS: Overall, the results demonstrated a distinct longitudinal metabolomic pattern characterized by increases in circulating amino acids and time-dependent changes in carbohydrate- and lipid-related metabolites within the first 72 h of TPN. This exploratory, time-resolved metabolomic study in 37 patients highlights the utility of untargeted metabolomics for characterizing early metabolic adaptation to parenteral nutrition and supporting postoperative metabolic monitoring.